The goals of this project are to determine the mechanism of action and species susceptibility to 3-methylindole (3MI)-induced lung injury. Specific objectives include the development of an effective prevention for acute bovine pulmonary edema (ABPE) and assessment of the risk of exposure to 3MI in man. Previous work has shown that 3MI causes selective cytotoxicity to Type 1 and Clara cells in the lung as a consequence of it's metabolism by mixed function oxidase system. Various inhibitors and conjugating agents can modify the covalent binding and in-vivo toxicity of 3MI. We plan to investigate the effect of glutathione and cysteine on covalent binding of 14C-3MI, in-vivo and attempt to identify reaction products between 3MI metabolites and these agents. Studies will also be conducted to identify tissue and urinary metabolites of 3MI and develop assay procedures for these compounds. Other studies will involve goat lung cytochrome P-450, the possible role of epoxide hydrolase, and the effect of additional inducers and inhibitors on the severity of 3MI-induced lung injury. Experiments are being initiated on assay and enzymology of the bacterial enzyme responsible for decarboxylation of indoleacetic acid to 3MI.